We have currently recruited and successfully screened, enrolled and completed 17 Parkinson's disease patients for the current study. The patients tolerated the drug administration generally well and no unusual physical or behavioral side effects have been encountered. However, several (2) patients were not able to tolerate the highest doses of nicotine and did not receive the full dose-response curve during the acute phase. Only one subject did not tolerate the full chronic phase. Positive effects of acute administration of nicotine appear to be in several areas including arousal/attention, motor speed, and processing speed. Potential negative effects appear in the area of hand tracking performance. Little effect appeared in divided attention, the Stroop task, or in semantic retrieval. Positive chronic effects of nicotine appeared in all motor performance task including the Pronation/Supination task, the Stand/Walk/Sit task, and the Finger Dexterity task. There was marginally statistically significant improvement on the Choice Reaction Time task, mainly seen in the motor component. Particularly interesting is the persistence of some of the effects of nicotine even several weeks after the cessation of drug administration. Now that we have demonstrated the feasibility of administering nicotine both acutely and chronically to PD patients and that nicotine appears to have quantifiable benefits to motoric and cognitive performance, it is reasonable to propose two further studies to confirm and extend these results: 1) it is necessary to perform an extended double-blind placebo controlled trial using chronic nicotine by patch to establish whether the preliminary results seen in the open chronic phase of this trial are confirmed under more rigorous conditions; 2) it may be worthwhile to consider whether nicotine administration to very early PD patients might delay the progression of symptoms to the point where dopamine therapy is necessary. This was the model used in the pivotal selegiline trial (DATTOP Study) that established that selegiline appeared to delay the time to onset of severe enough symptoms to require dopamine precursor therapy. Finally, our results provide support for the development of more selective and potent nicotinic agonists as augmentative or monotherapy for PD. Such agents should reach clinical trial shortly.